Electron dense metal complexes will be synthesized and their binding to selected sites on biopolymers investigated. Polymercurimethanes will be allowed to react with sulfur atoms, incorporated either as phosphorothioate or as thiolate derivatives, at base specific sites in polynucleotides. Polymercurimethanes having reactive organic substituents for attachment to specific amino acids will be prepared and their protein binding properties examined. The resulting labeled biopolymers will be studied in the transmission electron microscope or scanning transmission electron microscope to detect the heavy atom labels. The method could be applied to elucidate the structures of diverse biological aggregates such as nuceleosomes, viruses, and nitrogenase and for gene mapping. Platinum metallointercalation reagents could be used to probe the nature of the intercalation process, widely invoked for drug binding and as a key factor in protein-nucleic acid recognition. Special emphasis will be given to a newly developed reagent having twice the thickness (6.3 A) of a normal intercalator, to polyintercalators, and to metallointercalator derivatized columns for polynucleotide processing. Studies of the antitumor drug cis-DDP and related platinum complexes will be conducted. Drug binding to chromatin and to closed circular and linear DNAs will be investigated in kinetic experiments. The ammonia release hypothesis, devised to account for differences in drug action for cis- versus trans-DDP, will be tested. Platinum-nucleotide and -oligonucleotide complexes will be isolated and studied by NMR spectroscopy in solution and by x-ray crystallography in the solid state. New platinum complexes synthesized in this work, including the metallointercalators, will be routinely screened for antitumor and antibiotic activities.